| Structural highlights
Function
[BACE1_HUMAN] Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
We describe a novel series of potent inhibitors of human beta-secretase. These compounds possess the hydroxyethyl amine transition state isostere. A 2.5A crystal structure of inhibitor 32 bound to BACE is provided.
Design of potent inhibitors of human beta-secretase. Part 1.,Freskos JN, Fobian YM, Benson TE, Bienkowski MJ, Brown DL, Emmons TL, Heintz R, Laborde A, McDonald JJ, Mischke BV, Molyneaux JM, Moon JB, Mullins PB, Bryan Prince D, Paddock DJ, Tomasselli AG, Winterrowd G Bioorg Med Chem Lett. 2007 Jan 1;17(1):73-7. Epub 2006 Oct 4. PMID:17046251[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lin X, Koelsch G, Wu S, Downs D, Dashti A, Tang J. Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1456-60. PMID:10677483
- ↑ Okada H, Zhang W, Peterhoff C, Hwang JC, Nixon RA, Ryu SH, Kim TW. Proteomic identification of sorting nexin 6 as a negative regulator of BACE1-mediated APP processing. FASEB J. 2010 Aug;24(8):2783-94. doi: 10.1096/fj.09-146357. Epub 2010 Mar 30. PMID:20354142 doi:10.1096/fj.09-146357
- ↑ Freskos JN, Fobian YM, Benson TE, Bienkowski MJ, Brown DL, Emmons TL, Heintz R, Laborde A, McDonald JJ, Mischke BV, Molyneaux JM, Moon JB, Mullins PB, Bryan Prince D, Paddock DJ, Tomasselli AG, Winterrowd G. Design of potent inhibitors of human beta-secretase. Part 1. Bioorg Med Chem Lett. 2007 Jan 1;17(1):73-7. Epub 2006 Oct 4. PMID:17046251 doi:10.1016/j.bmcl.2006.09.092
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